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Interaction between metabolism and transport of toxicological-relevant substances in the gastrointestinal barrier
11/2015-11/2018
This third-party funded project is conducted in the framework of the BfR research programme on modern methods in toxicology.
DFG grant number: LA1177/4-4
Project homepage: -
Project description:
Polycyclic aromatic hydrocarbons (PAHS) comprise a large group of organic compounds whose structure consists of at least two condensed aromatic rings. In their original form, PAHs are lipophilic, slightly reactive compounds which are only converted into reactive substances through the intercellular metabolism. The International Agency for Research on Cancer (IARC) has categorised 15 PAHs as carcinogenic (Group1), probably carcinogenic (Group 2A) or possibly carcinogenic (Group 2B) to humans. Benzo[a]pyrene (BP) was classified as carcinogenic to humans in Group 1. The European Food Safety Authority (EFSA) regards eight PAHs as carcinogenic to humans if ingested with food.
The hepatobiliary excretion of BP was examined in vivo in the first application period. In this study, it was possible to confirm data which showed that various efflux transporters convey the excretion of BP and its metabolites from the body, but there are still many open questions regarding the influence of other PAHs on the bioavailability, metabolism, excretion and molecular effects of BP. There is a lack of data at the moment which represent in particular oral intake and the subsequent effects on the liver so that a better estimation can be made of the risk to humans posed by BP and mixtures thereof. It is of particularly great importance here to establish whether the carcinogenic potential of BP is over- or underestimated. The current project phase focuses on the characterisation of synergetic, additive or inhibitory effects compared to BP in mono exposure
Project partner:
- Biochemical Institute of Environmental Carcinogens, Germany
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